Toxicity from radiation therapy associated with abnormal transcriptional responses to DNA damage

AUTOR(ES)

Rieger, Kerri E.

FONTE

National Academy of Sciences

RESUMO

Toxicity from radiation therapy is a grave problem for cancer patients. We hypothesized that some cases of toxicity are associated with abnormal transcriptional responses to radiation. We used microarrays to measure responses to ionizing and UV radiation in lymphoblastoid cells derived from 14 patients with acute radiation toxicity. The analysis used heterogeneity-associated transformation of the data to account for a clinical outcome arising from more than one underlying cause. To compute the risk of toxicity for each patient, we applied nearest shrunken centroids, a method that identifies and cross-validates predictive genes. Transcriptional responses in 24 genes predicted radiation toxicity in 9 of 14 patients with no false positives among 43 controls (P = 2.2 × 10-7). The responses of these nine patients displayed significant heterogeneity. Of the five patients with toxicity and normal responses, two were treated with protocols that proved to be highly toxic. These results may enable physicians to predict toxicity and tailor treatment for individual patients.

Documentos Relacionados

• Characterization of radiation damage to DNA by reaction with borohydride.
• Physiological Responses of the Hyperthermophilic Archaeon “Pyrococcus abyssi” to DNA Damage Caused by Ionizing Radiation
• Deletion of Mouse Rad9 Causes Abnormal Cellular Responses to DNA Damage, Genomic Instability, and Embryonic Lethality
• Bone Marrow Toxicity Associated with 5-Fluorocytosine Therapy
• Portrait of transcriptional responses to ultraviolet and ionizing radiation in human cells